Catheter assemblies for neuromodulation proximate a bifurcation of a renal artery and associated systems and methods

ABSTRACT

Catheter assemblies for neuromodulation proximate a renal artery bifurcation and associated systems and methods are disclosed herein. A catheter assembly configured in accordance with a particular embodiment of the present technology can include a shaft having a proximal portion, a distal portion, and two therapeutic arms extending from the distal portion. The shaft can be configured to deliver the distal portion to a treatment site proximate a branch point or bifurcation in a renal blood vessel. The therapeutic arms can include energy delivery elements that are configured to deliver the therapeutically-effective energy to renal nerves proximate the branch point.

TECHNICAL FIELD

The present technology relates generally to neuromodulation therapies.In particular, several embodiments of the present technology aredirected to catheter assemblies for neuromodulation proximate abifurcation of a renal artery and associated methods and systems.

BACKGROUND

The sympathetic nervous system (SNS) is a primarily involuntary bodilycontrol system typically associated with stress responses. Fibers of theSNS innervate tissue in almost every organ system of the human body andcan affect characteristics such as pupil diameter, gut motility, andurinary output. Such regulation can have adaptive utility in maintaininghomeostasis or preparing the body for rapid response to environmentalfactors. Chronic activation of the SNS, however, is a common maladaptiveresponse that can drive the progression of many disease states.Excessive activation of the renal SNS in particular has been identifiedexperimentally and in humans as a likely contributor to the complexpathophysiology of hypertension, states of volume overload (such asheart failure), and progressive renal disease. For example, radiotracerdilution has demonstrated increased renal norepinephrine (“NE”)spillover rates in patients with essential hypertension.

Cardio-renal sympathetic nerve hyperactivity can be particularlypronounced in patients with heart failure. For example, an exaggeratedNE overflow from the heart and kidneys of plasma is often found in thesepatients. Heightened SNS activation commonly characterizes both chronicand end stage renal disease. In patients with end stage renal disease,NE plasma levels above the median have been demonstrated to bepredictive of cardiovascular diseases and several causes of death. Thisis also true for patients suffering from diabetic or contrastnephropathy. Evidence suggests that sensory afferent signals originatingfrom diseased kidneys are major contributors to initiating andsustaining elevated central sympathetic outflow.

Sympathetic nerves innervating the kidneys terminate in the bloodvessels, the juxtaglomerular apparatus, and the renal tubules.Stimulation of the renal sympathetic nerves can cause increased reninrelease, increased sodium (Na+) reabsorption, and a reduction of renalblood flow. These neural regulation components of renal function areconsiderably stimulated in disease states characterized by heightenedsympathetic tone and likely contribute to increased blood pressure inhypertensive patients. The reduction of renal blood flow and glomerularfiltration rate as a result of renal sympathetic efferent stimulation islikely a cornerstone of the loss of renal function in cardio-renalsyndrome (i.e., renal dysfunction as a progressive complication ofchronic heart failure). Pharmacologic strategies to thwart theconsequences of renal efferent sympathetic stimulation include centrallyacting sympatholytic drugs, beta blockers (intended to reduce reninrelease), angiotensin converting enzyme inhibitors and receptor blockers(intended to block the action of angiotensin II and aldosteroneactivation consequent to renin release), and diuretics (intended tocounter the renal sympathetic mediated sodium and water retention).These pharmacologic strategies, however, have significant limitationsincluding limited efficacy, compliance issues, side effects, and others.Recently, intravascular devices that reduce sympathetic nerve activityby applying an energy field to a target site in the renal artery (e.g.,via radiofrequency (RF) ablation) have been shown to reduce bloodpressure in patients with treatment-resistant hypertension.

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present disclosure can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale. Instead, emphasis is placed on illustratingclearly the principles of the present disclosure. Furthermore,components can be shown as transparent in certain views for clarity ofillustration only and not to indicate that the illustrated component isnecessarily transparent.

FIG. 1 is a partially schematic diagram of a neuromodulation systemconfigured in accordance with an embodiment of the present technology.

FIG. 2 illustrates modulating renal nerves with a catheter configured inaccordance with an embodiment of the present technology.

FIGS. 3A-3C are a partial cross-sectional views of a distal portion of acatheter assembly being delivered and deployed proximate a renal arterybifurcation in accordance with an embodiment of the present technology.

FIG. 4 is a partial cross-sectional view of a distal portion of acatheter assembly proximate a renal artery bifurcation in accordancewith an embodiment of the present technology.

FIGS. 5A and 5B are a partial cross-sectional views of a distal portionof a catheter assembly being delivered and deployed proximate a renalartery bifurcation in accordance with another embodiment of the presenttechnology.

FIG. 6 is a partial cross-sectional view of a distal portion of acatheter assembly proximate a renal artery bifurcation in accordancewith another embodiment of the present technology.

FIG. 7 is a partial cross-sectional view of a distal portion of acatheter assembly proximate a renal artery bifurcation in accordancewith a further embodiment of the present technology.

FIGS. 8A and 8B are a partial cross-sectional views of a distal portionof a catheter assembly being delivered and deployed proximate a renalartery bifurcation in accordance with a further embodiment of thepresent technology.

FIG. 9 is a partial cross-sectional view of a distal portion of acatheter assembly proximate a renal artery bifurcation in accordancewith yet another embodiment of the present technology.

FIG. 10 is a partial cross-sectional view of a distal portion of acatheter assembly proximate a renal artery bifurcation in accordancewith an additional embodiment of the present technology.

FIG. 11 is a partial cross-sectional view of a distal portion of aninter-to-extravascular catheter assembly proximate a renal arterybifurcation in accordance with an embodiment of the present technology.

FIG. 12 is a partial cross-sectional view of a distal portion of amulti-vessel catheter assembly for neuromodulation within a renal arteryand a renal vein proximate a renal artery bifurcation in accordance withan embodiment of the present technology.

FIG. 13 is a conceptual illustration of the SNS and how the braincommunicates with the body via the SNS.

FIG. 14 is an enlarged anatomic view of nerves innervating a left kidneyto form the renal plexus surrounding the left renal artery.

FIGS. 15 and 16 provide anatomic and conceptual views of a human body,respectively, depicting neural efferent and afferent communicationbetween the brain and kidneys.

FIGS. 17 and 18 show the arterial vascular system and venous system ofthe human body, respectively.

DETAILED DESCRIPTION

The present technology is directed to apparatuses, systems, and methodsfor achieving electrically- and/or thermally-induced renalneuromodulation (i.e., rendering neural fibers that innervate the kidneyinert or inactive or otherwise completely or partially reduced infunction) by percutaneous transluminal intravascular access. Inparticular, at least some embodiments of the present technology relateto catheters and catheter assemblies having therapeutic arms thatdeliver therapeutically-effective energy to renal nerves proximate arenal artery bifurcation. In other embodiments, the present technologymay be used to apply ablative energy proximate (i.e., at or near) abifurcation or branch point in other blood vessels and/or other organswithin the human body (e.g., the heart).

Specific details of several embodiments of the technology are describedbelow with reference to FIGS. 1-18. Although many of the embodiments aredescribed below with respect to devices, systems, and methods forintravascular modulation of renal nerves using multi-electrodetherapeutic assemblies, other applications and other embodiments inaddition to those described herein are within the scope of thetechnology. Additionally, several other embodiments of the technologycan have different configurations, components, or procedures than thosedescribed herein. A person of ordinary skill in the art, therefore, willaccordingly understand that the technology can have other embodimentswith additional elements, or the technology can have other embodimentswithout several of the features shown and described below with referenceto FIGS. 1-18.

As used herein, the terms “distal” and “proximal” define a position ordirection with respect to the treating clinician or clinician's controldevice (e.g., a handle assembly). “Distal” or “distally” are a positiondistant from or in a direction away from the clinician or clinician'scontrol device. “Proximal” and “proximally” are a position near or in adirection toward the clinician or clinician's control device.

I. RENAL NEUROMODULATION

Renal neuromodulation is the partial or complete incapacitation or othereffective disruption of nerves innervating the kidneys. In particular,renal neuromodulation comprises inhibiting, reducing, and/or blockingneural communication along neural fibers (i.e., efferent and/or afferentnerve fibers) innervating the kidneys. It is believed that renal nervesreside in close proximity to renal arteries within the adventitia of therenal arteries or otherwise within approximately 1 cm of the renalartery medial wall. The renal nerves are distributed randomly around thecircumference of the renal artery. However, evidence suggests that therenal nerves congregate distal to the aorta and proximate (e.g., at ornear) bifurcations or branch points of the renal artery (i.e., points atwhich the renal artery splits into two or more lumens). Thisconcentration of renal nerves provides a relatively confined site atwhich therapeutically effective energy can be applied.

The incapacitation provided by neuromodulation can be long-term (e.g.,permanent or for periods of months, years, or decades) or short-term(e.g., for periods of minutes, hours, days, or weeks). Renalneuromodulation is expected to efficaciously treat several clinicalconditions characterized by increased overall sympathetic activity, andin particular conditions associated with central sympathetic overstimulation such as hypertension, heart failure, acute myocardialinfarction, metabolic syndrome, insulin resistance, diabetes, leftventricular hypertrophy, chronic and end stage renal disease,inappropriate fluid retention in heart failure, cardio-renal syndrome,and sudden death. The reduction of afferent neural signals contributesto the systemic reduction of sympathetic tone/drive, and renalneuromodulation is expected to be useful in treating several conditionsassociated with systemic sympathetic over activity or hyperactivity.Renal neuromodulation can potentially benefit a variety of organs andbodily structures innervated by sympathetic nerves. For example, areduction in central sympathetic drive may reduce insulin resistancethat afflicts patients with metabolic syndrome and Type II diabetics.Additionally, osteoporosis can be sympathetically activated and mightbenefit from the downregulation of sympathetic drive that accompaniesrenal neuromodulation. A more detailed description of pertinent patientanatomy and physiology is provided in Section VI below.

Various techniques can be used to partially or completely incapacitateneural pathways, such as those innervating the kidney. The purposefulapplication of energy (e.g., electrical energy, thermal energy) totissue by energy delivery element(s) can induce one or more desiredthermal heating effects on localized regions of the renal artery andadjacent regions of the renal plexus, which lay intimately within oradjacent to the adventitia of the renal artery. The purposefulapplication of the thermal heating effects can achieve neuromodulationalong all or a portion of the renal plexus.

The thermal heating effects can include both thermal ablation andnon-ablative thermal alteration or damage (e.g., via sustained heatingand/or resistive heating). Desired thermal heating effects may includeraising the temperature of target neural fibers above a desiredthreshold to achieve non-ablative thermal alteration, or above a highertemperature to achieve ablative thermal alteration. For example, thetarget temperature can be above body temperature (e.g., approximately37° C.) but less than about 45° C. for non-ablative thermal alteration,or the target temperature can be about 45° C. or higher for the ablativethermal alteration.

More specifically, exposure to thermal energy (heat) in excess of a bodytemperature of about 37° C., but below a temperature of about 45° C.,may induce thermal alteration via moderate heating of the target neuralfibers or of vascular structures that perfuse the target fibers. Incases where vascular structures are affected, the target neural fibersare denied perfusion resulting in necrosis of the neural tissue. Forexample, this may induce non-ablative thermal alteration in the fibersor structures. Exposure to heat above a temperature of about 45° C., orabove about 60° C., may induce thermal alteration via substantialheating of the fibers or structures. For example, such highertemperatures may thermally ablate the target neural fibers or thevascular structures. In some patients, it may be desirable to achievetemperatures that thermally ablate the target neural fibers or thevascular structures, but that are less than about 90° C., or less thanabout 85° C., or less than about 80° C., and/or less than about 75° C.Regardless of the type of heat exposure utilized to induce the thermalneuromodulation, a reduction in renal sympathetic nerve activity (RSNA)is expected.

Hypothermic effects may also provide neuromodulation. Cryotherapy, forexample, may be used to cool tissue at a target site to providetherapeutically-effective direct cell injury (e.g., necrosis), vascularinjury (e.g., starving the cell from nutrients by damaging supplyingblood vessels), and sublethal hypothermia with subsequent apoptosis.Exposure to cryotherapeutic cooling can cause acute cell death (e.g.,immediately after exposure) and/or delayed cell death (e.g., duringtissue thawing and subsequent hyperperfusion). Embodiments of thepresent technology can include cooling a structure at or near an innersurface of a renal artery wall such that proximate (e.g., adjacent)tissue is effectively cooled to a depth where sympathetic renal nervesreside. For example, the cooling structure is cooled to the extent thatit causes therapeutically effective, cryogenic renal-nerve modulation.Sufficiently cooling at least a portion of a sympathetic renal nerve isexpected to slow or potentially block conduction of neural signals toproduce a prolonged or permanent reduction in renal sympatheticactivity.

Cryotherapy has certain characteristics that can be beneficial forintravascular renal neuromodulation. For example, cryotherapiesgenerally operate at temperatures that cause cryotherapeutic applicatorsto adhere to moist tissue. This can be beneficial because it promotesstable, consistent, and continued contact during treatment. The typicalconditions of treatment can make this an attractive feature because, forexample, a patient can move during treatment, a catheter associated withan applicator can move, and/or respiration can cause the kidneys to riseand fall and thereby move the renal arteries. In addition, blood flow ispulsatile and causes the renal arteries to pulse. Adhesion associatedwith cryotherapeutic cooling also can be advantageous when treatingshort renal arteries in which stable intravascular positioning can bemore difficult to achieve.

II. SELECTED EMBODIMENTS OF NEUROMODULATION SYSTEMS

FIG. 1 illustrates a neuromodulation system 10 (“system 10”) configuredin accordance with an embodiment of the present technology. The system10 includes an intravascular catheter 12 operably coupled to an energygenerator or energy source 26 (e.g., an RF energy generator, acryotherapy console, etc.). The catheter 12 can include an elongatedshaft 16 having a proximal portion 18, a handle 34 at a proximal regionof the proximal portion 18, and a distal portion 20. The catheter 12 canfurther include a treatment section or therapeutic assembly 21 (shownschematically) at the distal portion 20 (e.g., attached to the distalportion 20, defining a section of the distal portion 20, etc.). Asexplained in further detail below, in certain embodiments thetherapeutic assembly 21 can include two elongated members or arms 25that each include at least one energy delivery element 24 (e.g., anelectrode). The therapeutic assembly 21 can be delivered proximate to abifurcation or branch point of a renal blood vessel (e.g., a renalartery) such that the arms 25 can each be positioned in separatebranches of the renal blood vessel. The energy delivery elements 24 canbe configured to deliver energy (e.g., RF energy, cryotherapeuticcooling, etc.) to the walls of the branched blood vessel and providetherapeutically-effective electrically- and/or thermally-induced renalneuromodulation at either side of the bifurcation (e.g., proximate aconcentration of renal nerves).

The catheter 12 can be electrically coupled to the energy source 26 viaa cable 28, and the energy source 26 (e.g., a RF energy generator) canbe configured to produce a selected modality and magnitude of energy fordelivery to the treatment site (e.g., proximate a renal arterybifurcation) via the energy delivery elements 24. A supply wire (notshown) can extend along the elongated shaft 16 or through a lumen in theshaft 16 to the energy delivery elements 24 and transmit the treatmentenergy to the energy delivery elements 24. In some embodiments, eachenergy delivery element 24 includes its own supply wire. In otherembodiments, however, two or more energy delivery elements 24 may beelectrically coupled to the same supply wire. A control mechanism 32,such as foot pedal or handheld remote control device, may be connectedto the energy source 26 to allow the clinician to initiate, terminateand, optionally, adjust various operational characteristics of theenergy source 26, including, but not limited to, power delivery. Theremote control device (not shown) can be positioned in a sterile fieldand operably coupled to the energy delivery elements 24, and can beconfigured to allow the clinician to selectively activate and deactivatethe energy delivery elements 24. In other embodiments, the remotecontrol device may be built into the handle assembly 34.

The energy source 26 can be configured to deliver the treatment energyvia an automated control algorithm 30 and/or under the control of aclinician. For example, the energy source 26 can include computingdevices (e.g., personal computers, server computers, tablets, etc.)having processing circuitry (e.g., a microprocessor) that is configuredto execute stored instructions relating to the control algorithm 30. Inaddition, the processing circuitry may be configured to execute one ormore evaluation/feedback algorithms 31, which can be communicated to theclinician. For example, the energy source 26 can include a monitor ordisplay 33 and/or associated features that are configured to providevisual, audio, or other indications of power levels, sensor data, and/orother feedback. The energy source 26 can also be configured tocommunicate the feedback and other information to another device, suchas a monitor in a catheterization laboratory.

In certain embodiments, the system 10 may be configured to deliver amonopolar electric field via the energy delivery elements 24. In suchembodiments, a neutral or dispersive electrode 38 may be electricallyconnected to the energy generator 26 and attached to the exterior of thepatient (e.g., as shown in FIG. 2). In other embodiments, the system 10can deliver a bipolar electric field via the energy delivery elements 24and/or other suitable forms of treatment energy, such as a combinationof monopolar and bipolar electric fields. Additionally, the system 10can include one or more sensors (not shown) located proximate to orwithin the energy delivery elements 24. For example, the system 10 caninclude temperature sensors (e.g., thermocouple, thermistor, etc.),impedance sensors, pressure sensors, optical sensors, flow sensors,and/or other suitable sensors connected to one or more supply wires (notshown) that transmit signals from the sensors and/or convey energy tothe energy delivery elements 24.

FIG. 2 (with additional reference to FIG. 1) illustrates modulatingrenal nerves with an embodiment of the system 10. The catheter 12provides access to a bifurcation or branch point of the renal artery RAthrough an intravascular path P, such as a percutaneous access site inthe femoral (as shown in FIG. 2), brachial, radial, or axillary arteryto a targeted treatment site within a respective renal artery RA. Asillustrated, a section of the proximal portion 18 of the shaft 16 isexposed externally of the patient. By manipulating the proximal portion18 of the shaft 16 from outside the intravascular path P, the clinicianmay advance the shaft 16 through the sometimes tortuous intravascularpath P and remotely manipulate the distal portion 20 of the shaft 16. Inthe embodiment illustrated in FIG. 2, the therapeutic assembly 21 isdelivered intravascularly to the treatment site using a guide wire 66.The distal end of the therapeutic assembly 21 may define a passagewayfor engaging the guide wire 66 for delivery of the catheter 12 usingover-the-wire (“OTW”) or rapid exchange (“RX”) techniques. At thetreatment site, the guide wire 66 can be removed and the therapeuticassembly 21 can transform or otherwise be moved to a deployedarrangement for delivering energy at the treatment site. In otherembodiments, the therapeutic assembly 21 may be delivered to thetreatment site within a guide sheath (not shown). When the therapeuticassembly 21 is at the target site, the guide sheath may be at leastpartially withdrawn or retracted and the therapeutic assembly 21 can betransformed into the deployed arrangement. In other embodiments, theshaft 16 may be steerable itself such that the therapeutic assembly 21may be delivered to the treatment site without the aid of the guide wire66 and/or guide sheath.

Image guidance, e.g., computed tomography (CT), fluoroscopy,intravascular ultrasound (IVUS), optical coherence tomography (OCT),intracardiac echocardiography (ICE), or another suitable guidancemodality, or combinations thereof, may be used to aid the clinician'spositioning and manipulation of the therapeutic assembly 21. Forexample, a fluoroscopy system (e.g., including a flat-panel detector,x-ray, or c-arm) can be rotated to accurately visualize and identify thesite of the renal artery bifurcation and its takeoff angle (i.e., theangle at which the branches extend distally from the renal artery RAwith respect to one another), which may be obscured in theanterior-posterior (A-P) plane. In other embodiments, the site of therenal artery bifurcation can be determined using IVUS, OCT, and/or othersuitable image mapping modalities that can correlate the site of thebifurcation with an identifiable anatomical structure (e.g., a spinalfeature) and/or a radiopaque ruler (e.g., positioned under or on thepatient) before delivering the catheter 12. Further, in someembodiments, image guidance components (e.g., IVUS, OCT) may beintegrated with the catheter 12 and/or run in parallel with the catheter12 to provide image guidance during positioning of the therapeuticassembly. For example, image guidance components (e.g., IVUS or OCT) canbe coupled to at least one of the therapeutic assembly 21 (e.g.,proximal to the therapeutic arms 25) to provide three-dimensional imagesof the vasculature proximate the bifurcation to facilitate positioningor deploying the therapeutic arms 25 within the correct branches of theRA or elsewhere proximate the bifurcation.

As discussed in greater detail below, after the therapeutic assembly 21is delivered to the renal artery RA the arms 25 (FIG. 1) can bepositioned in respective branches of the renal artery RA and the energydelivery elements 24 (FIG. 1) can be placed proximate to (e.g., incontact with) vessel walls of the branched renal artery (e.g., using ashaped stylus, guide wires, magnets, etc.). Energy is then purposefullyapplied via the energy delivery elements 24 to vessel walls to induceone or more desired neuromodulating effects on localized regions of therenal artery proximate the renal artery bifurcation and adjacent regionsof the renal plexus RP, which lay intimately within, adjacent to, or inclose proximity to the adventitia of the renal artery RA. The purposefulapplication of the energy may achieve neuromodulation along all or atleast a portion of the renal plexus at both sites of the bifurcation.

The neuromodulating effects are generally a function of, at least inpart, power, time, contact between the energy delivery elements 24(FIG. 1) and the vessel wall, and blood flow through the vessel. Theneuromodulating effects may include denervation, thermal ablation,and/or non-ablative thermal alteration or damage (e.g., via sustainedheating and/or resistive heating). Desired thermal heating effects mayinclude raising the temperature of target neural fibers above a desiredthreshold to achieve non-ablative thermal alteration, or above a highertemperature to achieve ablative thermal alteration. For example, thetarget temperature may be above body temperature (e.g., approximately37° C.) but less than about 45° C. for non-ablative thermal alteration,or the target temperature may be about 45° C. or higher for the ablativethermal alteration. Desired non-thermal neuromodulation effects mayinclude altering the electrical signals transmitted in a nerve.

III. CATHETER ASSEMBLIES FOR NEUROMODULATION WITH THERAPEUTIC ARMS

FIG. 3A is a partial cross-sectional view of a distal portion of acatheter assembly 300 being delivered to a treatment site proximate abifurcation or branch point B of a renal artery RA in accordance with anembodiment of the present technology, and FIGS. 3B and 3C are partialcross-sectional views of the distal portion of the catheter assembly 300of FIG. 3A deployed at the treatment site in accordance with embodimentsof the present technology. As shown in FIGS. 3A-3C, the catheterassembly 300 can include a first catheter or elongated shaft 302 a and asecond catheter or shaft 302 b (referred to collectively as “shafts302”) having distal portions 304 a and 304 b, respectively, and proximalportions (not shown). The distal portion 304 a of the first shaft 302 acan be defined at least in part by a first therapeutic member or arm 306a, and the distal portion 304 b of the second shaft 302 b can be definedat least in part by a second therapeutic member or arm 306 b. The firstand second therapeutic arms 306 a and 306 b can include first and secondenergy delivery elements 308 a and 308 b, respectively (referred tocollectively as “energy delivery elements 308”), configured to delivertherapeutically-effective energy to a treatment site. The first andsecond arms 306 a and 306 b can be configured to be delivered proximatethe bifurcation B of the renal artery RA at least partially intocorresponding first and second branches BR1 and BR2 (collectivelyreferred to as “branches BR”) of the renal artery RA. The therapeuticarms 306 a and 306 b and the corresponding energy delivery elements 308a and 308 b carried thereon can define a therapeutic assembly configuredto modulate renal nerves proximate the bifurcation B of the renal arteryRA.

The shafts 302 can be made from relatively flexible materials (e.g.,polymers) to navigate the sometimes tortuous vasculature proximate therenal arteries, and the distal portions 304 may include braided and/orother semi-rigid structures that can support the therapeutic arms 306.The shafts 302 can be relatively small (e.g., microcatheters) such thatthey can be positioned together within the renal artery RA and,optionally, within a sheath or guide catheter 310 for delivery to therenal artery RA. In various embodiments, the proximal portions of thefirst and second shafts 302 a and 302 b can have a combined outerdiameter or cross-sectional dimension that is less than the innerdiameter or cross-sectional dimension of a guide catheter or sheath 310to allow both shafts 302 to be delivered through the guide catheter 310.For example, the guide catheter 310 may have a French size of 8 orsmaller (e.g., a 6 Fr guide catheter) to facilitate delivery into therenal artery RA, and the proximal portions of the outer diameters of theshafts 302 can be sized accordingly.

The distal portions 304 of the shafts 302 (e.g., the therapeutic arms306), however, can be delivered sequentially into the branches BR, andtherefore do not necessarily share the space within the guide catheter310. Accordingly, the distal portions 304 of the shafts 302 may havelarger outer cross-sectional dimensions or diameters than the outerdimensions of the proximal portions. In illustrated embodiment, forexample, the first and second therapeutic arms 306 a and 306 b havebulbous distal sections that carry the corresponding energy deliveryelements 308 a and 308 b. In other embodiments, however, the distalportions 304 of the shafts 302 can have other suitable enlargedconfigurations. In selected embodiments, for example, the shafts 302 canhave substantially uniform cross-sectional dimensions along theirlengths, and the energy delivery elements 308 can be made from a thickermaterial or structure (e.g., a larger diameter wire) to enlarge thecross-sectional dimensions of the distal portions 304 of the shafts 302.Such larger distal portions 304 can facilitate contact with adjacentvessel walls and may support larger energy delivery elements 308 (e.g.,larger electrodes). In further embodiments, one or both of the shafts302 can have substantially constant outer diameters along their proximaland distal portions. In still further embodiments, the guide catheter310 can include separate lumens configured to receive the first andsecond shafts 302 a or a separate guide catheter can be used for eachshaft 302 such the shafts 302 do not share the same cross-sectional areaand keep them spaced apart from one another. In selected embodiments, alumen of the guide catheter 310 (e.g., a dedicated lumen or the samelumen as is used to deliver the shafts 302) may be used to deliver imageguidance systems to the renal artery RA to facilitate positioning of thetherapeutic arms 306.

The energy delivery elements 308 may include one or more electrodespositioned along the length of the therapeutic arms 306. In theembodiment illustrated in FIGS. 3A-3C, for example, the energy deliveryelements 308 are coiled electrodes 316 positioned proximal to the distalends of the therapeutic arms 306, and formed from electricallyconductive wires wound around the respective shafts 302. The diameter ofthe wires can be selected based, at least in part, on the desiredthickness of each electrode 316 (e.g., thicker wire increases thediameter of the electrode 316) and/or the degree of energy transfer tobe provided by each electrode 316. In other embodiments, the energydelivery elements 308 can include other types of electrodes and/or theelectrodes 316 can be positioned elsewhere along the therapeutic arms306. For example, the energy delivery elements 308 can includecylindrical band electrodes extending around at least a portion of eachshaft 302, electrode tips having a bullet-like, spherical, and/or otheratraumatic shape at the distal ends of the shafts 302, and/or sphericalstructures positioned proximal of the distal tips of the shafts 302. Infurther embodiments, the energy delivery elements 308 can have othersuitable structures and/or multiple energy delivery elements 308 can beincluded on each therapeutic arm 306.

The energy delivery elements 308 can be configured to deliver varioustypes of energy to the target tissue. In certain embodiments, forexample, the energy delivery elements 308 can be configured to delivercontinuous or pulsed RF energy (e.g., at about 400-600 kHz) in amonopolar and/or bipolar electric field. When applied in a bipolarelectric field, the RF energy can be delivered across the twotherapeutic arms 306 (i.e., across the carina ridge of tissue betweenthe diverging vessels) between the first and second energy deliveryelements 308 a and 308 b. In other embodiments, the energy deliveryelements 308 can deliver RF energy independently of one another (i.e.,in a monopolar fashion using a passive electrode attached to the outsideof the patient), and the energy can be applied simultaneously,selectively, and/or sequentially. In embodiments including multipleenergy delivery elements 308 on the therapeutic arms 306, the energy maybe delivered between any desired combination of the energy deliveryelements 308, such as in a bipolar electric field across two electrodeson a single therapeutic arm 306, in a bipolar electric field across thetherapeutic arms 306, or selectively activated monopolar electricfields. This allows the clinician to select which energy deliveryelements 308 may be used for power delivery in order to form highlycustomized lesion(s) having a variety of shapes or patterns. The energydelivery elements 308 can also be configured to deliver microwaveenergy, various types of electric energy, direct current (DC),alternating current (AC), high or low voltage, pulsed or non-pulsed),sonic energy (e.g., ultrasound energy or high intensity ultrasound(HIFU) energy), electroporation, electromagnetic radiation energy (e.g.,infrared energy, laser energy, etc.), and/or other suitable forms ofenergy. For example, the energy delivery elements 308 can includeelectrodes specifically designed for electroporation and configured topulse a high voltage electric field across the bifurcation B thatprovides electroporation-induced neuromodulation at the target site andcan leave neighboring cells substantially unaffected. In otherembodiments the energy delivery elements 308 can include RF electrodesthat apply electric pulses across the bifurcation B, and thereby providea combination of thermal ablation and electroporation. In furtherembodiments, the energy delivery elements 308 may be configured toprovide direct thermal energy to the vessel walls using hot or cooledfluids (e.g., cryogenic cooling elements), hot or cooled elements,and/or thermoelectric effects (e.g., the Peltier effect). For example,the energy delivery elements 308 can be cryogenic applicators (e.g.,cryoprobes and/or cryoballoons) that deliver therapeutically-effectivecooling to the treatment site for neuromodulation.

As shown in FIG. 3A, the catheter assembly 300 can be delivered to thetreatment site (e.g., proximate the bifurcation B of the renal arteryRA) using the guide catheter 310 and first and second guide wires 312 aand 312 b (collectively referred to as guide wires 312) corresponding tothe first and second shafts 302 a and 302 b. The guide catheter 310 canbe inserted through the vasculature to the renal RA, and the first guidewire 312 a can be advanced through the guide catheter 310 into the firstbranch BR1 of the renal artery RA, and the first shaft 302 a can bepassed through the guide catheter 310 along the first guide wire 312 a(e.g., via a guide wire lumen extending through the first shaft 302 a)such that the first therapeutic arm 306 a extends beyond the bifurcationB at least partially into the first branch BR1. Similarly, the secondshaft 302 b can be advanced through the guide catheter 310 over thesecond guide wire 312 b (e.g., through a guide wire lumen) at leastpartially into the second branch BR2 of the renal artery RA. In otherembodiments, the first shaft 302 a and the second shaft 302 b caninclude or be attached to steerable members (e.g., pull wires) that canbe used to navigate the shafts 302 to the treatment site. In variousembodiments, the distal ends of the shafts 302 can include tapered oratraumatic tips 315 that can gently contact and/or deflect off of vesselwalls as the shafts 302 navigate through vasculature to the treatmentsite.

As best seen in FIG. 3B, once the energy delivery elements 308 arepositioned at their respective target sites within the branches BR ofthe renal artery RA, the guide wires 312 (FIG. 3A) can be removed fromat least the distal portions 304 of the shafts 302, and the energydelivery elements 308 can be positioned at the vessel walls of thebranches BR extending distally from the bifurcation B. The distalportions 304 of the shafts 302 can include magnets 314 that areconfigured to interact (e.g., attract) one another, and thereby draw theenergy delivery elements 308 towards one another to facilitatepositioning the energy delivery elements 308 proximate to (e.g., incontact with) the vessel walls extending distally from the bifurcationB. In the embodiment illustrated in FIG. 3B, the magnets 314 areproximal to the energy delivery elements 308 along the outer diametersof the shafts 302. In other embodiments, the magnets 314 can extendalong the inner diameters of the shafts 302, be embedded in the shafts302, be positioned within or distal to the energy delivery elements 308,and/or be positioned elsewhere along the shafts 302 that facilitatesdrawing the energy delivery elements 308 toward one another into contactwith the vessel walls. The positioning of the magnets 314 and thestrength of the magnetic field therebetween can be configured to accountfor the distance between the magnets 314 when positioned at thetreatment (e.g., the distance between the branches BR) and/or otheranatomical features (e.g., blood flow). In various embodiments, theguide wires 312 (FIG. 3A) can restrict the interaction of the magnets314 during delivery of the catheter assembly 300, and removing the guidewires 312 (FIG. 3A) can allow the magnets 314 to attract the shafts 302toward one another. In further embodiments, the magnets 314 can beconfigured to repel one another such that the energy delivery elements308 are positioned proximate to or contact the vessel walls of thebranches BR spaced apart from the bifurcation B.

The energy delivery elements 308 can also be drawn together and held incontact with the inner surfaces of the vessel walls using other suitablestructures and devices. For example, the guide catheter 310, a separatecatheter, or a sleeve (e.g., positioned within the guide catheter 310)can be advanced over both the first and second shafts 302 a and 302 btoward the bifurcation B to press the energy delivery elements 308toward one another. Pre-shaped stylets (not shown) can be advancethrough the shaft 302 (e.g., via a guide wire lumen) after the guidewires 312 (FIG. 3A) have been removed to deflect the energy deliveryelements 308 toward each other. In other embodiments, magnetic wires(not shown; e.g., wires having a magnetic core) can be advanced throughthe shafts 302 after the guide wires 312 (FIG. 3A) have been removed,and the magnetic field of the complementary magnetic wires can draw theenergy delivery elements 308 together. The magnetic wires can includemagnetic sections that extend along relatively short portions of thewires (e.g., only along the length of the energy delivery elements 308when aligned therewith), or the magnetic sections can extend alonglonger portions of the length (e.g., several centimeters proximal to theenergy delivery elements 308) to draw proximal portions of the shafts302 together. As described in greater detail below, in other embodimentsthe energy delivery elements 308 can be drawn together using variousother techniques.

Once the energy delivery elements 308 are positioned proximate to thevessel walls at the treatment site, the energy delivery elements 308 candeliver therapeutically-effective energy to modulate nerves proximatethe bifurcation B of the renal artery RA. Since the renal nerves may beconcentrated at or proximate to the carina of the bifurcation B (e.g.,as compared to proximal portions of the renal artery RA proximate theaorta), the catheter assembly 300 is expected to provide neuromodulationto a large portion of the renal nerves at a single, confined treatmentsite. In addition, the neuromodulation energy is delivered to renalnerves from both sides of the bifurcation B, and therefore may provide agreater concentration of therapeutically-effective energy to a largerpercentage of the renal nerves. For example, as shown in FIG. 3B, eachenergy delivery element 308 can deliver energy to a neuromodulation ortreatment zone 318 proximate a bifurcation. In the illustratedembodiment, the treatment zones 318 of the first and second energydelivery elements 308 a and 308 b overlap to form a continuous treatmentzone 318 at the carina of the renal artery bifurcation B (e.g., whichmay include a dense concentration of renal nerves). In otherembodiments, however, the treatment zones 318 can be discrete. Forexample, the energy delivery elements 308 may be substantially alignedwith one another within the branches BR as shown in FIG. 3B, but thetreatment zones 318 of the individual energy delivery elements 308 maybe smaller than those shown in FIG. 3B such that they do not overlap. Asshown in FIG. 3C, in further embodiments the energy delivery elements308 and corresponding treatment zones 318 can be offset from one anotheralong a longitudinal axis A-A of the renal artery RA. For example, thefirst energy delivery element 308 a can be advanced further along theaxis A-A into the first branch BR1 than the second energy deliveryelement 308 b such that the first energy delivery element 308 a ispositioned distal to the second energy delivery element 308 b relativeto the bifurcation B. The corresponding treatment zones 318 aretherefore also offset from one another along the axis A-A of the renalartery RA and deliver neuromodulation energy to discrete portions of thebranches BR. The offset energy delivery elements 308 can alternativelybe configured to deliver sufficient neuromodulation energy to formoffset, but overlapping, treatment zones 318.

In certain embodiments, a single energy delivery element 308 can beconfigured to deliver sufficient energy for neuromodulation proximatethe bifurcation B. For example, the first energy delivery element 308 acan deliver RF energy in a monopolar energy field that modulates renalnerves across the entire treatment zone 318 shown in FIG. 3B. In thisembodiment, the second shaft 302 b does not necessarily include anactive energy delivery element, but can include a mechanism (e.g., themagnet 314) to facilitate drawing the first energy delivery element 308a toward the vessel wall (e.g., to contact the vessel wall). In otherembodiments, the second shaft 302 b can be omitted, and a pre-shapedstylet, deflectable tip, and/or other suitable mechanism may be used tofacilitate positioning or wall contact for the first energy deliveryelement 308 a.

FIG. 4 is a partial cross-sectional view of a distal portion of acatheter assembly 400 deployed proximate a bifurcation B of a renalartery RA in accordance with another embodiment of the presenttechnology. The catheter assembly 400 can include a number of featuresgenerally similar to the features of the catheter assembly 300 describedabove with reference to FIGS. 3A-3C. For example, the catheter assembly400 can include first and second catheters or shafts 402 a and 402 b(referred to collectively as “shafts 402”) that include correspondingfirst and second therapeutic arms 406 a and 406 b, respectively(referred to collectively as “therapeutic arms 406”), configured toextend into the branches BR of the renal artery RA proximate thebifurcation B. The therapeutic arms 406 can each include one or moreenergy delivery elements 408 (identified individually as a first energydelivery element 408 a and a second energy delivery element 408 b), suchas spherical tip electrodes 420 at the distal ends of the therapeuticarms 406.

In the illustrated embodiment, the therapeutic arms 406 further includecoil structures 422 positioned proximal to the tip electrodes 420 andconfigured to generate complementary electromagnetic fields (e.g., via acurrent delivered across the coil structures 422). The electromagneticfield can attract the tip electrodes 420 toward one another tofacilitate contact with the vessel walls of the branches BR and enhanceenergy delivery. In other embodiments, one of the therapeutic arms 406can include the coil structure 422 and the other therapeutic arm 406 mayinclude a complimentary magnet or ferromagnetic material attracted tothe coil structure 422 when an electromagnetic field is applied acrossit. In certain embodiments, the electromagnetic field generated by thecoil structure(s) 422 can be strong enough to move the branches BR ofthe renal artery RA toward one another (e.g., as indicated by thearrows). In this embodiment, the energy can be concentrated to a moreconfined treatment zone that may include a higher density of renalnerves (e.g., because the nerves proximate the branches BR areconstricted into a smaller area).

FIGS. 5A and 5B are partial cross-sectional views of a distal portion ofa catheter 500 being delivered proximate a bifurcation B of a renalartery RA in accordance with another embodiment of the presenttechnology. The catheter 500 can include several features generallysimilar to the features of the catheter assemblies 300 and 400 describedabove with reference to FIGS. 3A-4. For example, the catheter 500 caninclude first and second energy delivery elements 508 a and 508 b(referred to collectively as “energy delivery elements 508) carried bydistal first and second therapeutic arms 506 a and 506 b, respectively(referred to collectively as “therapeutic arms 506”), that extend beyondthe renal arty bifurcation B into respective branches BR. However, inthe embodiment illustrated in FIGS. 5A and 5B, the therapeutic arms 506are joined together at their proximal ends to a single shaft 502 (e.g.,rather extending from two separate catheters). As shown in FIGS. 5A and5B, the catheter assembly 500 with the bifurcated shaft 502 may have adeployed or open arrangement in which the therapeutic arms 506 extenddistally from one another at an angle θ_(c) that at least generallycorresponds to an angle θ_(b) of the bifurcation B of the renal arteryRA to facilitate entry into the branches BR. In other embodiments, theangle θ_(c) between the therapeutic arms 506 can be less than thetakeoff angle θ_(b) of the bifurcation B such that the distal endportions of the therapeutic arms 506 can be positioned in the ostium ofthe individual branches BR and pushed apart from one another as thetherapeutic arms 506 are advanced distally into the correspondingbranches BR. This configuration can force the therapeutic arms 506 andthe energy delivery elements 508 positioned thereon against the adjacenttissue of the vessel wall to facilitate wall contact for energydelivery. In further embodiments, the angle θ_(c) between thetherapeutic arms 506 can be larger than the takeoff angle θ_(b).

Referring to FIG. 5A, during delivery of the catheter assembly 500, aguide catheter or sheath 510 can be advanced into the renal artery RA(e.g., at or near the ostium of the renal artery RA) and first andsecond guide wires 512 a and 512 b (referred to collectively as “guidewires 512”) can be advanced into each branch BR of the renal artery RA.The proximal ends (not shown) of the first and second guide wires 512 aand 512 b can then be positioned in the corresponding first and secondtherapeutic arms 506 a and 506 b, and the shaft 502 can be advanced overthe guide wires 512 to the renal artery RA. At the renal artery RA, thetherapeutic arms 506 can advance beyond the distal opening of the guidecatheter 510, and the first and second guide wires 512 a and 512 b candirect the therapeutic arms 506 beyond the carina of the bifurcation Binto the corresponding first and section branches BR1 and BR2 of therenal artery RA. In certain embodiments, the therapeutic arms 506 may beconfigured to deflect to the open configuration (e.g., with the angleθ_(c) between the therapeutic arms 506) when they are removed from theguide catheter 510 to track over the guide wires 512 positioned in thebranches BR.

Referring to FIG. 5B, the energy delivery elements 508 can be drawntoward each other after the guide wires 512 are removed. In certainembodiments, pre-shaped stylets or wires with magnetic distal cores canbe advanced through the shaft 502 after guide wire removal to facilitatepositioning the energy delivery elements 508 at least proximate to thevessel walls of the branches BR. In other embodiments, the therapeuticarms 506 can have a pre-shaped bias that directs the energy deliveryelements 508 into proximity or contact with the vessel walls. In thisembodiment, the guide wires 512 (FIG. 5A) can direct or force the firsttherapeutic arm 506 a and/or the second therapeutic arm 506 b into ashape that facilitates entry into the corresponding branches BR (e.g., agenerally straight shape). Once the therapeutic arms 506 are positionedat the target site (e.g., within the branches BR), the guide wires 512may be removed from the therapeutic arms 506 to allow the therapeuticarms 506 to revert to their pre-shaped bias and contact the vesselwalls. In further embodiments, the energy delivery elements 508 can bedrawn toward one another using magnets positioned along the shaft 502,electromagnetic fields, and/or other suitable mechanisms that facilitatewall contact. Once wall contact has been made, the energy deliveryelements 508 can apply therapeutically-effective energy to discrete oroverlapping treatment zones to both sides of the concentration of renalnerves proximate the bifurcation B.

FIG. 6 is a partial cross-sectional view of a distal portion of acatheter assembly 600 proximate a bifurcation B of a renal artery RA inaccordance with yet another embodiment of the present technology. Thecatheter assembly 600 can include a number of features generally similarto the features of the catheter assembly 500 described above withreference to FIGS. 5A and 5B. However, in the embodiment illustrated inFIG. 6, the catheter assembly 600 includes a woven or mesh structure 624that extends distally from a shaft 602. The mesh structure 624 caninclude a first therapeutic arm 606 a and a second therapeutic arm 606 b(referred to collectively as “therapeutic arms 606”), which carrycorresponding first and second energy delivery elements 608 a and 608 b,respectively (referred to collectively as “energy delivery elements608”). The therapeutic arms 606 can be defined by distally projectingportions of the mesh structure 624 or the body of the mesh structure624.

In certain embodiments, the mesh structure 624 may be movable ortransformable between a delivery or low-profile state (e.g., a radiallycollapsed mesh structure) that allows the mesh structure 624 to bedelivered into the renal artery RA, and a deployed or expanded state(e.g., radially expanded) as shown in FIG. 6 after delivery to the renalartery RA. In the deployed state, the therapeutic arms 606 can extend atleast partially into the branches BR and can be shaped such that theenergy delivery elements 608 contact a portion of the vessel wallproximate the bifurcation B. The mesh structure 624 can be selectivelytransformable between the delivery and deployed states by manipulating apull wire (not shown) that extends through the shaft 602, via automaticdeployment using an actuator (e.g., on a remote control or on a proximalhandle (not shown) of the catheter assembly 600), and/or other suitabledeployment techniques. For example, the mesh structure 624 can includeone or more braided wires that are not joined at the intersections and apull wire attached at a distal portion of the mesh structure 624. Thepull wire can be extended distally to contract or otherwise collapse themesh structure 624 during delivery and can be pulled proximally at thetreatment site to expand the mesh structure 624 to the configurationshown in FIG. 6. In certain embodiments, the mesh structure 624 can becollapsed or retracted (e.g., via a pull wire) after it has beenpositioned proximate the bifurcation B to draw the energy deliveryelements 608 toward one another to enhance wall contact. In otherembodiments, the mesh structure 624 can be made from a relativelyflexible or soft material and have a cylindrical shape such that it canbe delivered in an elongated or collapsed cylindrical shape and thenexpanded radially outwardly at the target site and pressed against thebifurcation B to wrap around the bifurcation B and extend into thebranches BR.

FIG. 7 is a partial cross-sectional view of a distal portion of acatheter assembly 700 configured in accordance with a further embodimentof the present technology. The catheter assembly 700 includes severalfeatures generally similar to the features of the catheter assemblies500 and 600 described above with reference to FIGS. 5A-6, such as firstand second energy delivery elements 708 a and 708 b carried by first andsecond therapeutic arms 706 a and 706 b, respectively, that extenddistally from a single shaft 702. In the embodiment illustrated in FIG.7, the catheter assembly 700 further includes a pull line 726 (partiallyshown in broken lines) connected to distal end sections of thetherapeutic arms 706 (e.g., at or near the energy delivery elements 708)and extending through the shaft 702 to a proximal end portion where itcan be manipulated by a clinician. The pull line 726 can be made from aflexible wire material, a polymer material (e.g., as used for sutures),and/or other suitable materials. A clinician can manipulate the proximalend portion of the pull line 726 (e.g., by pulling it proximally) topull or bend the energy delivery elements 708 toward one another andinto stable contact against the vessel walls of the branches BR. Incertain embodiments, the therapeutic arms 706 may be biased toward oneanother by a braided structure, laser-cut hypotubes (e.g., polymer ormetal hypotubes), shape memory material (e.g., nitinol), and/or othersuitable biased structures integrated with the therapeutic arms 706. Insuch embodiments, the biased therapeutic arms 706 can be urged towardone another by the pull line 726 by pulling it proximally.

As further shown in FIG. 7, the catheter assembly 700 may also includean expandable member 728 (e.g., an inflatable balloon) at the shaft 702proximal to the bifurcation B of the shaft 702. The expandable member728 can be delivered to the renal artery RA in a collapsed orlow-profile delivery state and expanded to at least partially occludethe renal artery RA. For example, the expandable member 728 can beinflated with a gas (e.g., air or expanded refrigerant) and/or a liquid(e.g., saline solution, cooled fluid, etc.). The occlusion provided bythe expandable member 728 can reduce or eliminate blood flow through thebranches BR of the renal artery RA during energy delivery, and isexpected to reduce the sometimes variable operational characteristicscaused by blood flow. The expandable member 728 can also anchor thedistal portion of the catheter assembly 700 in the renal artery RA tofacilitate positioning the therapeutic arms 706 by stabilizing the shaft702 in the renal artery RA and/or centering the shaft 702 in the renalartery RA. The expandable member 728 is an optional component that maynot be included in some embodiments.

FIGS. 8A and 8B are a partial cross-sectional views of a distal portionof a catheter assembly 800 being delivered and deployed proximate arenal artery bifurcation B in accordance with an additional embodimentof the present technology. The catheter assembly 800 can include anumber of features generally similar to the features of the catheterassemblies 500, 600, and 700 described above with reference to FIGS.5A-7. In the illustrated embodiment, however, first and secondtherapeutic arms 806 a and 806 b (collectively referred to as“therapeutic arms 806”) are coupled together at a joint 830 (e.g., ahinged joint) at a distal end portion of a shaft 802. The joint 830 isconfigured to allow the therapeutic arms 806 to pivot, rotate, orotherwise move from a closed or delivery state (FIG. 8A) to an open ordeployed state (FIG. 8B) via remote activation, physical manipulation ofone or more pull lines (e.g., attached to the distal ends of thetherapeutic arms 806 and moved proximally or distally to move thetherapeutic arms 806 toward or away from the bifurcation B), and/orother suitable actuators known to those skilled in the art for closingand opening joints. In the closed arrangement shown in FIG. 8A, innersurfaces 834 of the therapeutic arms 806 can abut one another such thatthe distal end portion of the catheter assembly 800 has a substantiallylow profile that facilitates intravascular delivery. In the openarrangement shown in FIG. 8B, the therapeutic arms 806 can splay at anangle to form a gap or space 834 sized and shaped to receive the carinaof the bifurcation B such that the therapeutic arms 806 extend at leastpartially into the branches BR. Once positioned around the bifurcationB, the therapeutic arms 806 can be closed (e.g., as indicated by thearrows shown in FIG. 8B) to contact at least a portion of the innersurfaces 834 with the adjacent vessel walls.

In certain embodiments, the first and second therapeutic arms 806 a and806 b can be made from a conductive material (e.g., a platinum iridiumalloy) such that the entire jaw-like structure is electrically activatedand serves as energy delivery elements 808. In other embodiments,portions of the therapeutic arms 806 include an insulated covering(e.g., via a polymer covering), or the therapeutic arms 806 may becomposites of an insulative material and a conductive material. In theseembodiments, discrete portions 836 (shown in broken lines in FIG. 8B) ofeach therapeutic arm 806 facing the inner walls can be electricallyactivated to serve as the energy delivery elements 808 and applytherapeutically-effective energy proximate the bifurcation B.

FIG. 9 is a partial cross-sectional view of a distal portion of acatheter assembly 900 proximate a renal artery bifurcation B inaccordance with an additional embodiment of the present technology. Thecatheter assembly 900 can include a number of features generally similarto the features of the catheter assemblies described above. As shown inFIG. 9, however, rather than a bifurcated shaft, the catheter assembly900 includes a shaft 902 that extends into a single first therapeuticarm 906 a, which may be positioned within the first branch BR1 via aguide wire (not shown) as described above. The first therapeutic arm 906a can include a deflectable tip 938 and carries a first energy deliveryelement 908 a (e.g., an electrode). The shaft 902 can further include anaperture or port 940 proximal to the first therapeutic arm 908 a throughwhich a second arm 906 b carrying a second energy delivery element 908 bcan extend. The second arm 906 b can be made from a pre-shaped member(e.g., a wire) that is bent or otherwise formed at its distal section tofacilitate positioning the second electrode 908 b at least proximate thearterial wall extending distally from the bifurcation B. For example,the second arm 906 b can be made from a shape memory material (e.g.,nitinol), an electroactive polymer (e.g., a piezoelectric material),and/or other suitable shapeable materials. In various embodiments, thesecond therapeutic arm 906 b can be at least partially retracted intothe shaft 902 via the aperture 940 (e.g., as indicated by the arrowsshown in FIG. 9) during intravascular delivery. The second therapeuticarm 906 b may include an atraumatic tip (e.g., the tapered atraumatictip 315 shown in FIGS. 3A-3C) to gently contact the vessel walls as itis inserted into and retracted from the second branch BR2. At the renalartery RA, the second therapeutic arm 906 b may be advanced distallythrough the aperture 940 until it is positioned within the second branchBR2 proximate the bifurcation B. The first and second therapeutic arms906 a and 906 b may also include magnets and/or other suitablemechanisms to draw the energy delivery elements 908 toward thebifurcation B in alignment with one another or offset from one another.

As further shown in FIG. 9, the catheter assembly 900 can alsooptionally include an expandable member 942 (e.g., an inflatableballoon) at the second therapeutic arm 906 b proximal to the secondenergy delivery element 908 b. When energy is delivered in a bipolarelectric field, the expandable member 942 can be used to at leastpartially occlude blood flow through the second branch BR2, and therebyinhibit or interrupt electrical current that may flow through the blood.This forces the current path through the adventitia of the branches BRwhere the concentration of renal nerves lies, and therefore enhancesneuromodulation. To enhance cooling effects typically provided by theflowing blood, the catheter assembly 900 can be configured to deliver(e.g., inject) a cooling fluid (e.g., saline) proximate the secondenergy delivery element 908 b before or during energy delivery. Theexpandable member 942 may also be used to anchor or stabilize the secondtherapeutic arm 906 b during energy delivery and/or to press or bias thesecond energy delivery element 908 into contact with the vessel wall. Inother embodiments, the expandable member 942 can be at the firsttherapeutic arm 906 b proximal to the first energy delivery element 908a and/or the catheter assembly 900 can include more than one expandablemember 942.

FIG. 10 is a partial cross-sectional view of a distal portion of acatheter assembly 1000 configured in accordance with yet anotherembodiment of the present technology. The catheter assembly 1000includes features generally similar to the features of the catheterassemblies described above. In the embodiment illustrated in FIG. 10,however, first and second therapeutic arms 1006 a and 1006 b (referredto collectively as “therapeutic arms 1006”) each include deflectable tipportion 1044 distal to an energy delivery element 1008 (identified as afirst energy delivery element 1008 a and a second energy deliveryelement 1008 b) and a semi-rigid or flexible portion 1046 proximal tothe energy delivery element 1008. The deflectable tip portions 1044 canbe highly flexible and/or soft to deflect off of vessel walls and easedelivery of the therapeutic arms 1006 into the branches BR. The flexibleportion 1046 can be stiffer than the deflectable tip portions 1044 toforce or otherwise position the energy delivery elements 1008 in stablecontact against the vessel walls extending distally the bifurcation B.For example, in certain embodiments, the flexible portions 1046 can bemade from a pre-shaped wire configured to direct the energy deliveryelements 1008 toward one another in accordance with the vascularstructure proximate the bifurcation B. The first and second therapeuticarms 1006 a and 1006 b may be positioned simultaneously within therespective branches BR of the renal artery RA, or each therapeutic arm1006 may be inserted separately. Once positioned against the vesselwalls, the energy delivery elements 1008 can delivertherapeutically-effective energy to the nerves proximate the bifurcationB. When the energy delivery elements 1008 are configured to deliverenergy in the form of a bipolar energy field, the catheter assembly 1000may also include a return electrode 1048 electrically coupled to theenergy delivery elements 1008 at a distal portion of shaft 1002.

IV. NEUROMODULATION CATHETER ASSEMBLIES FOR INTRA-TO-EXTRAVASCULARDELIVERY

FIG. 11 is a partial cross-sectional view of a distal portion of acatheter assembly 1100 proximate a renal artery bifurcation B andconfigured in accordance with another embodiment of the presenttechnology. The catheter assembly 1100 includes several featuresgenerally similar to the catheters described above. However, as shown inFIG. 11, the catheter assembly 1100 includes a single therapeutic arm1106 extending from a shaft 1102 and carrying an energy delivery element1108. The therapeutic arm 1106 can be delivered to the treatment siteusing a guide wire or steerable features integrated with the therapeuticarm 1106. At the treatment site, the therapeutic arm 1106 can beconfigured to deliver the energy delivery element 1108 from a lumen ofthe renal artery RA (e.g., the one of the branches BR) into adventia ofthe renal artery RA or to an extravascular space proximate the carina ofthe bifurcation B. For example, the therapeutic arm 1106 can include acannula 1150 through which a needle (not shown) can extend to punctureor otherwise form a small opening through at least a portion of thevessel wall proximate the bifurcation B. The energy delivery element1108 (e.g., an electrode made of a flexible bundle of coils) can then bedelivered through the cannula 1150 into the adventitia of the vesselwall or extravascular space proximate the bifurcation B to apply energyto the proximal nerves. In other embodiments, the catheter assembly 1100can include other suitable structures for delivering the energy deliveryelement 1108 through the vessel walls into the extravascular space.Additional features related to intra-to-extravascular energy deliveryare disclosed in commonly-assigned U.S. Pat. No. 7,620,451, filed onFeb. 27, 2006, and entitled “METHODS AND APPARATUS FOR PULSED ELECTRICFIELD NEUROMODULATION VIA AN INTRA-TO-EXTRAVASCULAR APPROACH,” which isherein incorporated by reference in its entirety.

In certain embodiments, the catheter assembly 1100 can include a secondtherapeutic arm (not shown) generally similar to the therapeutic arm1106 shown in FIG. 11. The second therapeutic arm can be configured toprovide extravascular neuromodulation via an opposite branch BR1 as thetherapeutic arm 1106, and therefore provide extravascularneuromodulation at both sides of the bifurcation B. In otherembodiments, the therapeutic arm 1106 can be combined with any of theintravascular therapeutic arms described above to deliverneuromodulation energy to both sides of the bifurcation B. The catheterassembly 1100 can alternatively include a second shaft or arm that doesnot include an energy delivery element, but includes a feature, such asa magnet, that is configured to draw the energy delivery element 1108and the cannula 1150 toward a vessel wall extending from the bifurcationB to facilitate access to the adventitia and/or extravascular spaceproximate the bifurcation B.

V. NEUROMODULATION CATHETER ASSEMBLIES FOR MULTI-VESSEL DELIVERY

FIG. 12 is a partial cross-sectional view of a distal portion of acatheter assembly 1200 configured in accordance with a furtherembodiment of the present technology. The catheter assembly 1200includes features generally similar to the features of the catheterassemblies described above, such as first and second therapeutic arms1206 a and 1206 b (referred to collectively as “therapeutic arms 1206)carrying first and second energy delivery elements 1208 a and 1208 b,respectively (referred to collectively as “energy delivery elements1208”), for therapeutically-effective modulation of nerves proximate abifurcation or branch point of a vessel (e.g., the bifurcation B of therenal artery RA). However, in the embodiment illustrated in FIG. 12,each therapeutic arm 1206 defines a distal portion of a separatecatheter or shaft 1202 a or 1202 b (identified individually as a firstshaft 1202 a and a second shaft 1202 b, and referred to collectively as“shafts 1202”) configured to be delivered to different vessels proximatea bifurcation of at least one of the vessels. For example, as shown inFIG. 12, the distal portion of the first shaft 1202 a can be deliveredto the renal artery RA proximate the bifurcation B, and the distalportion of the second shaft 1202 b can be delivered to a renal vein (RV)proximate the bifurcation B of the renal artery RA. The first and secondenergy delivery elements 1208 a and 1208 b can be substantially alignedalong an arterial wall proximate the bifurcation B as shown in FIG. 12,or may be offset from one another at the vessel walls.

As further shown in FIG. 12, the therapeutic arms 1206 can includecomplimentary magnetic features 1252 (e.g., each magnetic feature 1252having a different polarity) proximate to the energy delivery elements1208. The magnetic features 1252 can draw the energy delivery element1208 toward one another against adjacent wall portions of the renalartery RA and the renal vein (RV) such that the energy delivery elements1208 can apply therapeutically effective energy on either site of thenerves between the renal artery RA and renal vein (RV proximate thebifurcation B. In certain embodiments, one of the magnetic features 1252includes two poles such that the magnetic features 1252 (and thereforethe therapeutic arms 1206) repel one another as they are advancedthrough the vasculature toward the treatment site (e.g., proximate thebifurcation B). Once both therapeutic arms 1206 are at the treatmentsite, the shaft 1202 with the bipolar magnetic feature 1252 can berotated or otherwise manipulated such that the two magnetic features1252 are attracted to one another to draw the energy delivery elements1208 together for wall contact. In other embodiments, the catheterassembly 1200 can include other features that facilitate contact withthe walls of the renal artery RA and renal vein RV. The catheterassembly 1200, like the catheter assemblies described above, can applytherapeutically-effective energy to the concentration of nervesproximate the renal artery bifurcation B, and renal neuromodulation atsuch a region dense with renal nerves is expected to provide enhancedoverall neuromodulation effects.

It will be appreciated that specific embodiments of the technology havebeen described herein for purposes of illustration, but that variousmodifications may be made without deviating from the disclosure. Forexample, many of the catheter assemblies described above include twotherapeutic arms. However, any of the embodiments of the catheterassemblies can include a single therapeutic arm or more than twotherapeutic arms. If more than two therapeutic arms are included in acatheter assembly, each therapeutic arm can define a distal portion ofits own shaft, the therapeutic arms can extend from the same shaft, orthe shaft and/or therapeutic arms may include one or more apertures(e.g., similar to the port 940 shown in FIG. 9) from which one or moretherapeutic arms can be extended. In such multiple therapeutic armembodiments, more than one therapeutic arm can be positioned in eachbranch BR of the renal artery RA. For example, one or more therapeuticarms can face outwardly away from the bifurcation B and one or moreother therapeutic arms can face toward the bifurcation B. In otherembodiments, multiple arms can be positioned at different target sitesalong the length of each branch BR, thereby neuromodulating multiplezones within each branch BR. In further embodiments, catheter assembliescan include a therapeutic arm corresponding to each branch vesselextending from a branch point (e.g., three therapeutic arms configuredto be delivered to three branch vessels).

VI. PERTINENT ANATOMY AND PHYSIOLOGY

The following discussion provides further details regarding pertinentpatient anatomy and physiology. This section is intended to supplementand expand upon the previous discussion regarding the relevant anatomyand physiology, and to provide additional context regarding thedisclosed technology and the therapeutic benefits associated with renalmodulation. For example, as mentioned previously, several properties ofthe renal vasculature may inform the design of treatment devices andassociated methods for achieving renal neuromodulation via intravascularaccess, and impose specific design requirements for such devices.Specific design requirements may include accessing the renal artery,facilitating stable contact between the energy delivery elements of suchdevices and a luminal surface or wall of the renal artery, and/oreffectively modulating the renal nerves with the neuromodulatoryapparatus.

A. The Sympathetic Nervous System

The Sympathetic Nervous System (SNS) is a branch of the autonomicnervous system along with the enteric nervous system and parasympatheticnervous system. It is always active at a basal level (called sympathetictone) and becomes more active during times of stress. Like other partsof the nervous system, the sympathetic nervous system operates through aseries of interconnected neurons. Sympathetic neurons are frequentlyconsidered part of the peripheral nervous system (PNS), although manylie within the central nervous system (CNS). Sympathetic neurons of thespinal cord (which is part of the CNS) communicate with peripheralsympathetic neurons via a series of sympathetic ganglia. Within theganglia, spinal cord sympathetic neurons join peripheral sympatheticneurons through synapses. Spinal cord sympathetic neurons are thereforecalled presynaptic (or preganglionic) neurons, while peripheralsympathetic neurons are called postsynaptic (or postganglionic) neurons.

At synapses within the sympathetic ganglia, preganglionic sympatheticneurons release acetylcholine, a chemical messenger that binds andactivates nicotinic acetylcholine receptors on postganglionic neurons.In response to this stimulus, postganglionic neurons principally releasenoradrenaline (norepinephrine). Prolonged activation may elicit therelease of adrenaline from the adrenal medulla.

Once released, norepinephrine and epinephrine bind adrenergic receptorson peripheral tissues. Binding to adrenergic receptors causes a neuronaland hormonal response. The physiologic manifestations include pupildilation, increased heart rate, occasional vomiting, and increased bloodpressure. Increased sweating is also seen due to binding of cholinergicreceptors of the sweat glands.

The sympathetic nervous system is responsible for up- anddown-regulating many homeostatic mechanisms in living organisms. Fibersfrom the SNS innervate tissues in almost every organ system, providingat least some regulatory function to things as diverse as pupildiameter, gut motility, and urinary output. This response is also knownas sympatho-adrenal response of the body, as the preganglionicsympathetic fibers that end in the adrenal medulla (but also all othersympathetic fibers) secrete acetylcholine, which activates the secretionof adrenaline (epinephrine) and to a lesser extent noradrenaline(norepinephrine). Therefore, this response that acts primarily on thecardiovascular system is mediated directly via impulses transmittedthrough the sympathetic nervous system and indirectly via catecholaminessecreted from the adrenal medulla.

Science typically looks at the SNS as an automatic regulation system,that is, one that operates without the intervention of consciousthought. Some evolutionary theorists suggest that the sympatheticnervous system operated in early organisms to maintain survival as thesympathetic nervous system is responsible for priming the body foraction. One example of this priming is in the moments before waking, inwhich sympathetic outflow spontaneously increases in preparation foraction.

1. The Sympathetic Chain

As shown in FIG. 13, the SNS provides a network of nerves that allowsthe brain to communicate with the body. Sympathetic nerves originateinside the vertebral column, toward the middle of the spinal cord in theintermediolateral cell column (or lateral horn), beginning at the firstthoracic segment of the spinal cord and are thought to extend to thesecond or third lumbar segments. Because its cells begin in the thoracicand lumbar regions of the spinal cord, the SNS is said to have athoracolumbar outflow. Axons of these nerves leave the spinal cordthrough the anterior rootlet/root. They pass near the spinal (sensory)ganglion, where they enter the anterior rami of the spinal nerves.However, unlike somatic innervation, they quickly separate out throughwhite rami connectors which connect to either the paravertebral (whichlie near the vertebral column) or prevertebral (which lie near theaortic bifurcation) ganglia extending alongside the spinal column.

In order to reach the target organs and glands, the axons should travellong distances in the body, and, to accomplish this, many axons relaytheir message to a second cell through synaptic transmission. The endsof the axons link across a space, the synapse, to the dendrites of thesecond cell. The first cell (the presynaptic cell) sends aneurotransmitter across the synaptic cleft where it activates the secondcell (the postsynaptic cell). The message is then carried to the finaldestination.

In the SNS and other components of the peripheral nervous system, thesesynapses are made at sites called ganglia. The cell that sends its fiberis called a preganglionic cell, while the cell whose fiber leaves theganglion is called a postganglionic cell. As mentioned previously, thepreganglionic cells of the SNS are located between the first thoracic(T1) segment and third lumbar (L3) segments of the spinal cord.Postganglionic cells have their cell bodies in the ganglia and sendtheir axons to target organs or glands.

The ganglia include not just the sympathetic trunks but also thecervical ganglia (superior, middle and inferior), which sendssympathetic nerve fibers to the head and thorax organs, and the celiacand mesenteric ganglia (which send sympathetic fibers to the gut).

2. Innervation of the Kidneys

As shown in FIG. 14, the kidney is innervated by the renal plexus RP,which is intimately associated with the renal artery. The renal plexusRP is an autonomic plexus that surrounds the renal artery and isembedded within the adventitia of the renal artery. The renal plexus RPextends along the renal artery until it arrives at the substance of thekidney. Fibers contributing to the renal plexus RP arise from the celiacganglion, the superior mesenteric ganglion, the aorticorenal ganglionand the aortic plexus. The renal plexus RP, also referred to as therenal nerve, is predominantly comprised of sympathetic components. Thereis no (or at least very minimal) parasympathetic innervation of thekidney.

Preganglionic neuronal cell bodies are located in the intermediolateralcell column of the spinal cord. Preganglionic axons pass through theparavertebral ganglia (they do not synapse) to become the lessersplanchnic nerve, the least splanchnic nerve, first lumbar splanchnicnerve, second lumbar splanchnic nerve, and travel to the celiacganglion, the superior mesenteric ganglion, and the aorticorenalganglion. Postganglionic neuronal cell bodies exit the celiac ganglion,the superior mesenteric ganglion, and the aorticorenal ganglion to therenal plexus RP and are distributed to the renal vasculature.

3. Renal Sympathetic Neural Activity

Messages travel through the SNS in a bidirectional flow. Efferentmessages may trigger changes in different parts of the bodysimultaneously. For example, the sympathetic nervous system mayaccelerate heart rate; widen bronchial passages; decrease motility(movement) of the large intestine; constrict blood vessels; increaseperistalsis in the esophagus; cause pupil dilation, piloerection (goosebumps) and perspiration (sweating); and raise blood pressure. Afferentmessages carry signals from various organs and sensory receptors in thebody to other organs and, particularly, the brain.

Hypertension, heart failure and chronic kidney disease are a few of manydisease states that result from chronic activation of the SNS,especially the renal sympathetic nervous system. Chronic activation ofthe SNS is a maladaptive response that drives the progression of thesedisease states. Pharmaceutical management of therenin-angiotensin-aldosterone system (RAAS) has been a longstanding, butsomewhat ineffective, approach for reducing over-activity of the SNS.

As mentioned above, the renal sympathetic nervous system has beenidentified as a major contributor to the complex pathophysiology ofhypertension, states of volume overload (such as heart failure), andprogressive renal disease, both experimentally and in humans. Studiesemploying radiotracer dilution methodology to measure overflow ofnorepinephrine from the kidneys to plasma revealed increased renalnorepinephrine (NE) spillover rates in patients with essentialhypertension, particularly so in young hypertensive subjects, which inconcert with increased NE spillover from the heart, is consistent withthe hemodynamic profile typically seen in early hypertension andcharacterized by an increased heart rate, cardiac output, andrenovascular resistance. It is now known that essential hypertension iscommonly neurogenic, often accompanied by pronounced sympathetic nervoussystem overactivity.

Activation of cardiorenal sympathetic nerve activity is even morepronounced in heart failure, as demonstrated by an exaggerated increaseof NE overflow from the heart and the kidneys to plasma in this patientgroup. In line with this notion is the recent demonstration of a strongnegative predictive value of renal sympathetic activation on all-causemortality and heart transplantation in patients with congestive heartfailure, which is independent of overall sympathetic activity,glomerular filtration rate, and left ventricular ejection fraction.These findings support the notion that treatment regimens that aredesigned to reduce renal sympathetic stimulation have the potential toimprove survival in patients with heart failure.

Both chronic and end stage renal disease are characterized by heightenedsympathetic nervous activation. In patients with end stage renaldisease, plasma levels of norepinephrine above the median have beendemonstrated to be predictive for both all-cause death and death fromcardiovascular disease. This is also true for patients suffering fromdiabetic or contrast nephropathy. There is compelling evidencesuggesting that sensory afferent signals originating from the diseasedkidneys are major contributors to initiating and sustaining elevatedcentral sympathetic outflow in this patient group; this facilitates theoccurrence of the well known adverse consequences of chronic sympatheticover activity, such as hypertension, left ventricular hypertrophy,ventricular arrhythmias, sudden cardiac death, insulin resistance,diabetes, and metabolic syndrome.

(i) Renal Sympathetic Efferent Activity

Sympathetic nerves to the kidneys terminate in the blood vessels, thejuxtaglomerular apparatus and the renal tubules. Stimulation of therenal sympathetic nerves causes increased renin release, increasedsodium (Na+) reabsorption, and a reduction of renal blood flow. Thesecomponents of the neural regulation of renal function are considerablystimulated in disease states characterized by heightened sympathetictone and clearly contribute to the rise in blood pressure inhypertensive patients. The reduction of renal blood flow and glomerularfiltration rate as a result of renal sympathetic efferent stimulation islikely a cornerstone of the loss of renal function in cardio-renalsyndrome, which is renal dysfunction as a progressive complication ofchronic heart failure, with a clinical course that typically fluctuateswith the patient's clinical status and treatment. Pharmacologicstrategies to thwart the consequences of renal efferent sympatheticstimulation include centrally acting sympatholytic drugs, beta blockers(intended to reduce renin release), angiotensin converting enzymeinhibitors and receptor blockers (intended to block the action ofangiotensin II and aldosterone activation consequent to renin release)and diuretics (intended to counter the renal sympathetic mediated sodiumand water retention). However, the current pharmacologic strategies havesignificant limitations including limited efficacy, compliance issues,side effects and others.

(ii) Renal Sensory Afferent Nerve Activity

The kidneys communicate with integral structures in the central nervoussystem via renal sensory afferent nerves. Several forms of “renalinjury” may induce activation of sensory afferent signals. For example,renal ischemia, reduction in stroke volume or renal blood flow, or anabundance of adenosine enzyme may trigger activation of afferent neuralcommunication. As shown in FIGS. 15 and 16, this afferent communicationmight be from the kidney to the brain or might be from one kidney to theother kidney (via the central nervous system). These afferent signalsare centrally integrated and may result in increased sympatheticoutflow. This sympathetic drive is directed towards the kidneys, therebyactivating the RAAS and inducing increased renin secretion, sodiumretention, volume retention and vasoconstriction. Central sympatheticover activity also impacts other organs and bodily structures innervatedby sympathetic nerves such as the heart and the peripheral vasculature,resulting in the described adverse effects of sympathetic activation,several aspects of which also contribute to the rise in blood pressure.

The physiology therefore suggests that (i) modulation of tissue withefferent sympathetic nerves will reduce inappropriate renin release,salt retention, and reduction of renal blood flow, and that (ii)modulation of tissue with afferent sensory nerves will reduce thesystemic contribution to hypertension and other disease statesassociated with increased central sympathetic tone through its directeffect on the posterior hypothalamus as well as the contralateralkidney. In addition to the central hypotensive effects of afferent renaldenervation, a desirable reduction of central sympathetic outflow tovarious other sympathetically innervated organs such as the heart andthe vasculature is anticipated.

B. Additional Clinical Benefits of Renal Denervation

As provided above, renal denervation is likely to be valuable in thetreatment of several clinical conditions characterized by increasedoverall and particularly renal sympathetic activity such ashypertension, metabolic syndrome, insulin resistance, diabetes, leftventricular hypertrophy, chronic end stage renal disease, inappropriatefluid retention in heart failure, cardio-renal syndrome, and suddendeath. Since the reduction of afferent neural signals contributes to thesystemic reduction of sympathetic tone/drive, renal denervation mightalso be useful in treating other conditions associated with systemicsympathetic hyperactivity. Accordingly, renal denervation may alsobenefit other organs and bodily structures innervated by sympatheticnerves, including those identified in FIG. 13. For example, aspreviously discussed, a reduction in central sympathetic drive mayreduce the insulin resistance that afflicts people with metabolicsyndrome and Type II diabetics. Additionally, patients with osteoporosisare also sympathetically activated and might also benefit from the downregulation of sympathetic drive that accompanies renal denervation.

C. Achieving Intravascular Access to the Renal Artery

In accordance with the present technology, neuromodulation of a leftand/or right renal plexus RP, which is intimately associated with a leftand/or right renal artery, may be achieved through intravascular access.As FIG. 17 shows, blood moved by contractions of the heart is conveyedfrom the left ventricle of the heart by the aorta. The aorta descendsthrough the thorax and branches into the left and right renal arteries.Below the renal arteries, the aorta bifurcates at the left and rightiliac arteries. The left and right iliac arteries descend, respectively,through the left and right legs and join the left and right femoralarteries.

As FIG. 18 shows, the blood collects in veins and returns to the heart,through the femoral veins into the iliac veins and into the inferiorvena cava. The inferior vena cava branches into the left and right renalveins. Above the renal veins, the inferior vena cava ascends to conveyblood into the right atrium of the heart. From the right atrium, theblood is pumped through the right ventricle into the lungs, where it isoxygenated. From the lungs, the oxygenated blood is conveyed into theleft atrium. From the left atrium, the oxygenated blood is conveyed bythe left ventricle back to the aorta.

As will be described in greater detail later, the femoral artery may beaccessed and cannulated at the base of the femoral triangle justinferior to the midpoint of the inguinal ligament. A catheter may beinserted percutaneously into the femoral artery through this accesssite, passed through the iliac artery and aorta, and placed into eitherthe left or right renal artery. This comprises an intravascular paththat offers minimally invasive access to a respective renal arteryand/or other renal blood vessels.

The wrist, upper arm, and shoulder region provide other locations forintroduction of catheters into the arterial system. For example,catheterization of either the radial, brachial, or axillary artery maybe utilized in select cases. Catheters introduced via these accesspoints may be passed through the subclavian artery on the left side (orvia the subclavian and brachiocephalic arteries on the right side),through the aortic arch, down the descending aorta and into the renalarteries using standard angiographic technique.

D. Properties and Characteristics of the Renal Vasculature

Since neuromodulation of a left and/or right renal plexus RP may beachieved in accordance with the present technology through intravascularaccess, properties and characteristics of the renal vasculature mayimpose constraints upon and/or inform the design of apparatus, systems,and methods for achieving such renal neuromodulation. Some of theseproperties and characteristics may vary across the patient populationand/or within a specific patient across time, as well as in response todisease states, such as hypertension, chronic kidney disease, vasculardisease, end-stage renal disease, insulin resistance, diabetes,metabolic syndrome, etc. These properties and characteristics, asexplained herein, may have bearing on the efficacy of the procedure andthe specific design of the intravascular device. Properties of interestmay include, for example, material/mechanical, spatial, fluiddynamic/hemodynamic and/or thermodynamic properties.

As discussed previously, a catheter may be advanced percutaneously intoeither the left or right renal artery via a minimally invasiveintravascular path. However, minimally invasive renal arterial accessmay be challenging, for example, because as compared to some otherarteries that are routinely accessed using catheters, the renal arteriesare often extremely tortuous, may be of relatively small diameter,and/or may be of relatively short length. Furthermore, renal arterialatherosclerosis is common in many patients, particularly those withcardiovascular disease. Renal arterial anatomy also may varysignificantly from patient to patient, which further complicatesminimally invasive access. Significant inter-patient variation may beseen, for example, in relative tortuosity, diameter, length, and/oratherosclerotic plaque burden, as well as in the takeoff angle at whicha renal artery branches from the aorta. Apparatus, systems and methodsfor achieving renal neuromodulation via intravascular access shouldaccount for these and other aspects of renal arterial anatomy and itsvariation across the patient population when minimally invasivelyaccessing a renal artery.

In addition to complicating renal arterial access, specifics of therenal anatomy also complicate establishment of stable contact betweenneuromodulatory apparatus and a luminal surface or wall of a renalartery. When the neuromodulatory apparatus includes an energy deliveryelement, such as an electrode, consistent positioning and appropriatecontact force applied by the energy delivery element to the vessel wallare important for predictability. However, navigation is impeded by thetight space within a renal artery, as well as tortuosity of the artery.Furthermore, establishing consistent contact is complicated by patientmovement, respiration, and/or the cardiac cycle because these factorsmay cause significant movement of the renal artery relative to theaorta, and the cardiac cycle may transiently distend the renal artery(i.e., cause the wall of the artery to pulse).

Even after accessing a renal artery and facilitating stable contactbetween neuromodulatory apparatus and a luminal surface of the artery,nerves in and around the adventia of the artery should be safelymodulated via the neuromodulatory apparatus. Effectively applyingthermal treatment from within a renal artery is non-trivial given thepotential clinical complications associated with such treatment. Forexample, the intima and media of the renal artery are highly vulnerableto thermal injury. As discussed in greater detail below, theintima-media thickness separating the vessel lumen from its adventitiameans that target renal nerves may be multiple millimeters distant fromthe luminal surface of the artery. Sufficient energy should be deliveredto or heat removed from the target renal nerves to modulate the targetrenal nerves without excessively cooling or heating the vessel wall tothe extent that the wall is frozen, desiccated, or otherwise potentiallyaffected to an undesirable extent. A potential clinical complicationassociated with excessive heating is thrombus formation from coagulatingblood flowing through the artery. Given that this thrombus may cause akidney infarct, thereby causing irreversible damage to the kidney,thermal treatment from within the renal artery should be appliedcarefully. Accordingly, the complex fluid mechanics and thermodynamicconditions present in the renal artery during treatment, particularlythose that may impact heat transfer dynamics at the treatment site, maybe important in applying energy (e.g., heating thermal energy) and/orremoving heat from the tissue (e.g., cooling thermal conditions) fromwithin the renal artery.

The neuromodulatory apparatus should also be configured to allow foradjustable positioning and repositioning of the energy delivery elementwithin the renal artery since location of treatment may also impactclinical efficacy. For example, it may be tempting to apply a fullcircumferential treatment from within the renal artery given that therenal nerves may be spaced circumferentially around a renal artery. Insome situations, full-circle lesion likely resulting from a continuouscircumferential treatment may be potentially related to renal arterystenosis. Therefore, the formation of more complex lesions along alongitudinal dimension of the renal artery and/or repositioning of theneuromodulatory apparatus to multiple treatment locations may bedesirable. It should be noted, however, that a benefit of creating acircumferential ablation may outweigh the potential of renal arterystenosis or the risk may be mitigated with certain embodiments or incertain patients and creating a circumferential ablation could be agoal. Additionally, variable positioning and repositioning of theneuromodulatory apparatus may prove to be useful in circumstances wherethe renal artery is particularly tortuous or where there are proximalbranch vessels off the renal artery main vessel, making treatment incertain locations challenging. Manipulation of a device in a renalartery should also consider mechanical injury imposed by the device onthe renal artery. Motion of a device in an artery, for example byinserting, manipulating, negotiating bends and so forth, may contributeto dissection, perforation, denuding intima, or disrupting the interiorelastic lamina.

Blood flow through a renal artery may be temporarily occluded for ashort time with minimal or no complications. However, occlusion for asignificant amount of time should be avoided to prevent injury to thekidney such as ischemia. It could be beneficial to avoid occlusion alltogether or, if occlusion is beneficial to the embodiment, to limit theduration of occlusion, for example to 2-5 minutes.

Based on the above described challenges of (1) renal arteryintervention, (2) consistent and stable placement of the treatmentelement against the vessel wall, (3) effective application of treatmentacross the vessel wall, (4) positioning and potentially repositioningthe treatment apparatus to allow for multiple treatment locations, and(5) avoiding or limiting duration of blood flow occlusion, variousindependent and dependent properties of the renal vasculature that maybe of interest include, for example, (a) vessel diameter, vessel length,intima-media thickness, coefficient of friction, and tortuosity; Bdistensibility, stiffness and modulus of elasticity of the vessel wall;(c) peak systolic, end-diastolic blood flow velocity, as well as themean systolic-diastolic peak blood flow velocity, and mean/maxvolumetric blood flow rate; (d) specific heat capacity of blood and/orof the vessel wall, thermal conductivity of blood and/or of the vesselwall, and/or thermal connectivity of blood flow past a vessel walltreatment site and/or radiative heat transfer; (e) renal artery motionrelative to the aorta induced by respiration, patient movement, and/orblood flow pulsatility; and (f) the takeoff angle of a renal arteryrelative to the aorta. These properties will be discussed in greaterdetail with respect to the renal arteries. However, dependent on theapparatus, systems and methods utilized to achieve renalneuromodulation, such properties of the renal arteries, also may guideand/or constrain design characteristics.

As noted above, an apparatus positioned within a renal artery shouldconform to the geometry of the artery. Renal artery vessel diameter,D_(RA), typically is in a range of about 2-10 mm, with most of thepatient population having a D_(RA) of about 4 mm to about 8 mm and anaverage of about 6 mm. Renal artery vessel length, L_(RA), between itsostium at the aorta/renal artery juncture and its distal branchings,generally is in a range of about 5-70 mm, and a significant portion ofthe patient population is in a range of about 20-50 mm. Since the targetrenal plexus is embedded within the adventitia of the renal artery, thecomposite Intima-Media Thickness, IMT, (i.e., the radial outwarddistance from the artery's luminal surface to the adventitia containingtarget neural structures) also is notable and generally is in a range ofabout 0.5-2.5 mm, with an average of about 1.5 mm. Although a certaindepth of treatment is important to reach the target neural fibers, thetreatment should not be too deep (e.g., >5 mm from inner wall of therenal artery) to avoid non-target tissue and anatomical structures suchas the renal vein.

An additional property of the renal artery that may be of interest isthe degree of renal motion relative to the aorta, induced by respirationand/or blood flow pulsatility. A patient's kidney, which located at thedistal end of the renal artery, may move as much as 10 cm (4 inches)cranially with respiratory excursion. This may impart significant motionto the renal artery connecting the aorta and the kidney, therebyrequiring from the neuromodulatory apparatus a unique balance ofstiffness and flexibility to maintain contact between the thermaltreatment element and the vessel wall during cycles of respiration.Furthermore, the takeoff angle between the renal artery and the aortamay vary significantly between patients, and also may vary dynamicallywithin a patient, e.g., due to kidney motion. The takeoff anglegenerally may be in a range of about 30°-135°.

X. CONCLUSION

The above detailed descriptions of embodiments of the technology are notintended to be exhaustive or to limit the technology to the precise formdisclosed above. Although specific embodiments of, and examples for, thetechnology are described above for illustrative purposes, variousequivalent modifications are possible within the scope of thetechnology, as those skilled in the relevant art will recognize. Forexample, while steps are presented in a given order, alternativeembodiments may perform steps in a different order. The variousembodiments described herein may also be combined to provide furtherembodiments.

From the foregoing, it will be appreciated that specific embodiments ofthe technology have been described herein for purposes of illustration,but well-known structures and functions have not been shown or describedin detail to avoid unnecessarily obscuring the description of theembodiments of the technology. Where the context permits, singular orplural terms may also include the plural or singular term, respectively.

Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, B all of the items in thelist, or (c) any combination of the items in the list. Additionally, theterm “comprising” is used throughout to mean including at least therecited feature(s) such that any greater number of the same featureand/or additional types of other features are not precluded. It willalso be appreciated that specific embodiments have been described hereinfor purposes of illustration, but that various modifications may be madewithout deviating from the technology. Further, while advantagesassociated with certain embodiments of the technology have beendescribed in the context of those embodiments, other embodiments mayalso exhibit such advantages, and not all embodiments need necessarilyexhibit such advantages to fall within the scope of the technology.Accordingly, the disclosure and associated technology can encompassother embodiments not expressly shown or described herein.

I/We claim:
 1. A neuromodulation catheter assembly, comprising: a shafthaving a proximal portion and a distal portion, wherein the shaft isconfigured to deliver the distal portion to a treatment site proximate abranch point in a renal blood vessel; a first therapeutic arm extendingfrom the distal portion of the shaft, the first therapeutic arm having afirst energy delivery element; and a second therapeutic arm extendingfrom the distal portion of the shaft, the second therapeutic arm havinga second energy delivery element, wherein the first and second energydelivery elements are configured to be positioned proximate to vesselwalls on opposing sides of the branch point of the renal blood vesseland deliver therapeutically-effective energy to renal nerves proximatethe branch point.
 2. The neuromodulation catheter assembly of claim 1wherein: the shaft comprises a first shaft and a second shaft, the firsttherapeutic arm defining a distal section of the first shaft, and thesecond therapeutic arm defining a distal section of the second shaft;the first therapeutic arm is configured to be delivered into a firstbranch vessel extending distally from the branch point; the secondtherapeutic arm is configured to be delivered into a second branchvessel extending distally from the branch point, the first and secondbranch vessels having vessel walls extending distally from the branchpoint; the first energy delivery element is configured to apply thetherapeutically-effective energy to the vessel wall of the first branchvessel proximate the branch point; and the second energy deliveryelement is configured to apply the therapeutically-effective energy tothe vessel wall of the second branch vessel proximate the branch point.3. The neuromodulation catheter assembly of claim 2 wherein: the firstenergy delivery element is configured to be delivered to a firstposition in the first branch vessel; and the second energy deliveryelement is configured to be delivered to a second position in the secondbranch vessel, the second position being offset from the first positionwith respect to a longitudinal axis of the renal blood vessel.
 4. Theneuromodulation apparatus of claim 1 wherein the distal portion of theshaft bifurcates to define the first and second therapeutic arms.
 5. Theneuromodulation apparatus of claim 4 wherein the shaft forms an angle atthe bifurcation, and wherein the angle is generally similar to a takeoff angle of the branch point.
 6. The neuromodulation catheter assemblyof claim 1 wherein: the renal blood vessel is a renal artery with firstand second branches extending from the branch point in the renal artery;the first energy delivery element is configured to be delivered into thefirst branch and contact a vessel wall of the first branch; and thesecond energy delivery element is configured to be delivered into asecond branch and contact a vessel wall of the second branch.
 7. Theneuromodulation catheter assembly of claim 1, further comprising: afirst magnetic structure attached to the first therapeutic arm; and asecond magnetic structure attached to the second therapeutic arm,wherein the second magnet is configured to interact with the firstmagnet to draw the first and second energy delivery elements toward oneanother to contact vessel walls extending distally from the branchpoint.
 8. The neuromodulation catheter assembly of claim 1 wherein: thefirst therapeutic arm includes a first coil structure; the secondtherapeutic arm includes at least one of a second coil structure or amagnetic structure; and the first coil structure is configured togenerate an electromagnetic field complimentary to the magneticstructure or an electromagnetic field of the second coil structure suchthat the first and second energy delivery elements are drawn toward oneanother and into stable contact with vessel walls at least proximate thebranch point.
 9. The neuromodulation apparatus of claim 1, furthercomprising a mesh structure extending from the distal portion of theshaft, wherein the mesh structure defines the first and secondtherapeutic arms, and wherein the mesh structure is configured to extendat least partially around the branch point.
 10. The neuromodulationapparatus of claim 1, further comprising a pull line extending throughthe shaft and attached to distal end portions of the first and secondtherapeutic arms.
 11. The neuromodulation apparatus of claim 1, furthercomprising an expandable member extending from the distal portion of theshaft proximal to the first and second therapeutic arms, wherein theexpandable member is configured to at least substantially occlude therenal blood vessel.
 12. The neuromodulation apparatus of claim 1 whereinthe first therapeutic arm comprises an expandable member proximal to thefirst energy delivery element, and wherein the expandable member isconfigured to at least substantially occlude a branch vessel extendingfrom the renal blood vessel.
 13. The neuromodulation apparatus of claim1 wherein the first and second therapeutic arms are hinged together at ajoint proximal to the first and second energy delivery elements, thefirst and second therapeutic arms being configured to pivot about thejoint between an open position and a closed position, and whereinpivoting the first and second therapeutic arms to the open positiondefines a space configured to receive the branch point such that thefirst and second therapeutic arms extend distally around the branchpoint.
 14. The neuromodulation apparatus of claim 1 wherein: the distalportion of the shaft includes an opening proximal to the firsttherapeutic arm; and the second therapeutic arm retractably extendsthrough the opening.
 15. The neuromodulation apparatus of claim 1wherein the first therapeutic arm is configured to form an opening atleast proximate the branch point, and wherein the first energy deliveryelement is configured to deliver therapeutically-effective energy at theopening.
 16. The neuromodulation apparatus of claim 1 wherein at leastone of the first and second therapeutic arms includes a semi-rigidsection proximal to the first energy delivery element and a deflectablesection distal to the first energy delivery element.
 17. A renalneuromodulation catheter assembly, comprising: a shaft having a proximalportion and a distal portion, wherein the shaft is configured to deliverthe distal portion to a treatment site proximate a bifurcation in arenal artery; and a therapeutic arm extending from the distal portion ofthe shaft, the therapeutic arm having an energy delivery elementconfigured to apply therapeutically-effective energy at a treatment zoneat least proximate the bifurcation.
 18. The renal neuromodulationcatheter assembly of claim 17 wherein: the therapeutic arm is a firsttherapeutic arm configured to be delivered to a first branch of therenal artery; the energy delivery element is a first energy deliveryelement; the treatment zone is a first treatment zone at a first side ofthe bifurcation in the first branch of the renal artery; and thecatheter assembly further comprises a second therapeutic arm configuredto be delivered to a second branch of the renal artery, the secondtherapeutic arm having a second energy delivery element configured toapply therapeutically-effective energy at a second treatment zone at asecond side of the bifurcation in the second branch of the renal artery.19. The neuromodulation catheter assembly of claim 18 wherein: the shaftis a first shaft; and the neuromodulation catheter assembly furthercomprises a second shaft carrying the second therapeutic arm, the firstand second energy delivery elements being configured to contact vesselwalls of the corresponding first and second branches adjacent to thebifurcation.
 20. The neuromodulation catheter assembly of claim 18wherein the second therapeutic arm extends from the distal portion ofthe shaft.
 21. The neuromodulation catheter assembly of claim 17 whereinthe therapeutic arm comprises a cannula extending from a distal endportion, wherein the energy delivery element is configured to bedelivered at least partially through a vessel wall proximate thebifurcation via the cannula.
 22. The neuromodulation catheter assemblyof claim 17 wherein: the shaft is a first shaft; the therapeutic arm isa first therapeutic arm; the energy delivery element is a first energydelivery element configured to contact a vessel wall of the renal arteryspaced radially apart from the bifurcation; the treatment zone is afirst treatment zone; and the neuromodulation catheter assembly furthercomprises— a second shaft having a distal portion configured to bedelivered into a renal vein proximate the bifurcation of the renalartery; and a second therapeutic arm extending from the distal portionof the second shaft, the second therapeutic arm having a second energydelivery element configured to apply therapeutically-effective energy ata second treatment zone to a vessel wall facing toward the bifurcation.23. A method of treating a human patient, the method comprising:delivering a first therapeutic arm of a catheter assembly into a firstbranch proximate a branch point of a renal blood vessel; delivering asecond therapeutic arm of the catheter assembly into a second branch ofthe renal blood vessel proximate the branch point; directing the firstand second therapeutic arms toward one another such that a first energydelivery element carried by the first therapeutic arm is positionedproximate to a vessel wall of the first branch and a second energydelivery element carried by the second therapeutic arm is positionedproximate to a vessel wall of the second branch; and applyingtherapeutically-effective energy to target tissue via the first andsecond energy delivery elements.
 24. The method of claim 23 wherein:delivering the first therapeutic arm of the catheter assembly into thefirst branch comprises positioning the first energy delivery element ata first treatment site along a length of the first branch; anddelivering the second therapeutic arm of the catheter assembly into thesecond branch comprises positioning the second energy delivery elementat a second treatment site along a length of the second branch, whereinthe first and second sites are substantially aligned with one anotheralong a longitudinal axis of the renal blood vessel.
 25. The method ofclaim 23 wherein: delivering the first therapeutic arm of the catheterassembly into the first branch comprises positioning the first energydelivery element at a first treatment site along a length of the firstbranch; and delivering the second therapeutic arm of the catheterassembly into the second branch comprises positioning the second energydelivery element at a second treatment site along a length of the secondbranch, wherein the first and second sites are offset from one anotheralong a longitudinal axis of the renal blood vessel.
 26. The method ofclaim 23 wherein: delivering the first therapeutic arm of the catheterassembly into the first branch comprises delivering a distal portion ofa first catheter into the first branch; and delivering the secondtherapeutic arm of the catheter assembly into the second branchcomprises delivering a distal portion of a second catheter to the secondbranch.
 27. The method of claim 23 wherein delivering the first andsecond therapeutic arms of the catheter assembly into the first andsecond branch comprises delivering a distal portion of a bifurcatedshaft into the first and second branch.
 28. The method of claim 23,further comprising occluding the renal blood vessel during energydelivery.
 29. The method of claim 23 wherein delivering the first andsecond therapeutic arms of the catheter assembly into the first andsecond branch comprises pivoting the first and second therapeutic armsabout a joint proximate a distal end section of the therapeutic arms.30. The method of claim 23 wherein delivering the second therapeutic armof the catheter assembly into the second branch comprises extending thesecond therapeutic arm through an opening in a sidewall of a shaft,wherein the first therapeutic arm extends from a distal portion of theshaft.
 31. A method of treating a human patient, the method comprising:advancing a distal portion of a catheter assembly proximate abifurcation of a renal artery, wherein the catheter assembly includes atherapeutic arm carrying an energy delivery element extending from thedistal portion; engaging a vessel wall at the bifurcation with theenergy delivery element; and applying therapeutically-effective energyto renal nerves proximate the bifurcation using the energy deliveryelement.
 32. The method of claim 31 wherein applyingtherapeutically-effective energy to renal nerves proximate thebifurcation comprises applying therapeutically-effective energy to renalnerves from at least two treatment sites proximate the bifurcation. 33.The method of claim 31 wherein applying therapeutically-effective energyto renal nerves proximate the bifurcation comprises: applyingtherapeutically-effective energy to target tissue of the renal arteryfacing away from the bifurcation; and apply therapeutically-effectiveenergy to target tissue of a renal vein proximate facing the bifurcationand proximate to the bifurcation.